T细胞活化谱对脓毒症患者病原菌类型的鉴别效果

Clinical study on the types of pathogenic bacteria in sepsis patients based on T cell activation spectrum

目的探讨T细胞活化谱鉴别脓毒症不同病原菌感染中的临床价值。方法选取2020年9月至2022年6月于西安交通大学第一附属医院接受治疗的100例脓毒症患者作为脓毒症组,选取同期于门诊进行体检的37例健康志愿者作为对照组。脓毒症组根据患者入院病原学检查结果分为革兰氏阴性菌组(简称阴性菌组,46例)和革兰氏阳性菌组(简称阳性菌组,54例)。通过流式细胞仪检测患者外周血中T淋巴细胞的活化状态及其表面共刺激分子的表达情况。采用受试者操作特征(ROC)曲线评估CD38^(+)HLA-DR^(+)T细胞区分革兰氏阴性菌脓毒症和革兰氏阳性菌脓毒症的能力。结果阴性菌组和阳性菌组的外周血中CD4^(+)CD38^(+)CD69^(+)T细胞和CD8^(+)CD38^(+)CD69^(+)T细胞计数比较差异无统计学意义(P>0.05),但均高于对照组(P<0.05)。与对照组相比,脓毒症各亚组外周血中CD4^(+)CD38^(+)HLA-DR^(+)、CD8^(+)CD38^(+)HLA-DR^(+)T细胞计数显著增加(P<0.05),并且阴性菌组大于阳性菌组(P<0.05)。鉴别革兰氏阴性菌脓毒症和革兰氏阳性菌脓毒症时,CD4^(+)CD38^(+)HLA-DR^(+)T细胞的ROC曲线下面积(AUC)为0.901(95%CI 0.837~0.965),特异度为0.867,敏感度为0.836;CD8^(+)CD38^(+)HLA-DR^(+)T细胞的AUC为0.927(95%CI 0.872~0.982),特异度为0.778,敏感度为0.933。结论人白细胞DR抗原(HLA-DR)参与了脓毒症患者外周血中T细胞活化的关键免疫反应,并能区分脓毒症不同病原菌感染。

Objective To explore the clinical value of T-cell activation spectrum in differentiating sepsis from different pathogenic bacteria.Method From September 2020 to June 2022,100 patients with sepsis who were treated in The First Affiliated Hospital of Xi’an Jiaotong University were selected as the sepsis group,and 37 healthy volunteers who underwent physical examination in outpatient department were selected as the control group.Sepsis group was divided into two groups according to the pathogenic results of patients admitted to hospital:Gram-negative group(n=46)and Gram-positive group(n=54).The expression of T lymphocytes and surface costimulatory molecules in peripheral blood was detected by flow cytometry.The ability of CD38^(+)HLA-DR^(+)T cells to distinguish Gram-negative sepsis from Gram-positive sepsis was evaluated by the subject operating curve(ROC).Result The proportions of CD4^(+)CD38^(+)CD69^(+)T cells and CD8^(+)CD38^(+)CD69^(+)T cells in peripheral blood of each sepsis subgroup were higher than those of the control group(all P<0.05).There was no significant difference in the ratio of CD4^(+)CD38^(+)CD69^(+)T cells and CD8^(+)CD38^(+)CD69^(+)T cells between Gram-positive group and Gram-negative group(both P>0.05).Compared with the control group,the expression levels of CD4^(+)CD38^(+)HLA-DR^(+)and CD8^(+)CD38^(+)HLA-DR^(+)in peripheral blood of each sepsis subgroup were significantly increased(P<0.05),and the increase degree of Gram-negative group was greater than that of Gram-positive group(P<0.05).When distinguishing Gram-negative sepsis from Gram-positive sepsis,the AUC of CD4^(+)CD38^(+)HLA-DR^(+)T cells was 0.901(95%CI 0.837-0.965),the specificity was 0.867,and the sensitivity was 0.836;the AUC of CD8^(+)CD38^(+)HLA-DR^(+)T cells was 0.927(95%CI 0.872-0.982),the specificity was 0.778 and the sensitivity was 0.933.Conclusion HLA-DR is involved in the key immune response of T cell activation in the peripheral blood of sepsis patients,which can distinguish the infection of different pathogenic bacteria in sepsis.